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USMLE biochemistry > pyrimidine synthesis > Flashcards

pyrimidine synthesis Flashcards

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USMLE® Step 1 flashcards
1
Q

what is the chemical structure of pyrimidines and what are the different types ?

A

contains 1 carbon ring
cytosine
thymidine
uridine

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2
Q

how is UMP made ?

A

start off with glutamine
converted to carbamoyl phosphate
into orotic acid + PRPP
and then into UMP using UMP synthase

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3
Q

where is TMP and CMP derived from ?

A

derived from UMP

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4
Q

what is the enzyme that catalyzes the reaction between glutamine and carbamoyl synthase ?

A

carbamoyl synthetase II
CPS 2

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5
Q

what is the difference between CPS 1 and CCPS 2 ?

A

CPS 1 is found in the liver and is pat of the urea cycle
CPS 2 is involved in pyrimidine synthesis and is found in most cells

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6
Q

what disease is associated with a dysfunction in UMP synthase ?

A

orotic aciduria

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7
Q

what other disease is commonly confused with orotic aciduria ?

A

OTC deficiency

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8
Q

what is the main difference between orotic aciduria and OTC deficiency ?

A

raised ammonia levels in OT defeciency

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9
Q

what is the treatment for orotic aciduria ?

A

uridine

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10
Q

what are the clinical features associated with orotic aciduria ?

A

high levels off orotic acid in urine
megaloblastic anemia

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11
Q

when should i suspect orotic aciduria ?

A

in a baby with megaloblastic anemia that is not responding too folate treatment

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12
Q

what are the sources of the 1 ring formation in pyrimidines ?

A

carbamoyl phosphate
aspartate

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13
Q

what drug is associated with blocking the conversion of carbamoyl phosphate to orotic acid ?

A

leflunomide

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14
Q

what is the rate limiting enzyme for CPSII ?

A

UMP

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15
Q

what enzyme is inhibited by sulphonamides ?

A

dihydropteroate synthase this is in bacteria

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16
Q

what enzyme is inhibited by trimethoprim ?

A

dihydrofolate reductase this is in bacteria

17
Q

what drug blocks human dihydrofolate reductase ?

A

methotrexate

18
Q

by lab workup how can you differentiate between folate and vitamin b12 deficiency ?

A

both have a high level of homocystenuria
but there is a higher level of MMA in B12 deficiencies

19
Q

what is the clinical presentation of both b12 and folate deficiencies ?

A

folate - macrocytic anemia, neural tube defects
b12 - macrocytic anemia , neurological dysfunction ( causes demyelination )

20
Q

what is the role of folate in thee conversion of uridine into thymidine ?

A

N5. abd N10 tetrahydrofolate levels must be maintained iin order for the conversion to happen

21
Q

what is the other common phrase used to describe folate ?

A

1 carbon carrier

22
Q

what enzyme is blocked by the drug 5 FU ?

A

thymidlate synthase

23
Q

what enzyme is blocked by methotrexate ?

A

dihydrofolate reductasea

24
Q

how does 5 FU work as a chemotherapeutic agent ?

A

it mimics uracil
makes an abnormal dUMP
so no thymine is produced for cancer cells

25
Q

what are the sources of the 1 ring found in pyrimidines ?

A

carbamoyl phosphate and aspartate

26
Q

what enzyme is inhibited by the drug hydroxyurea ?

A

ribonucleotide redutase

27
Q

what enzyme is inhibited by leflunomide ?

A

dihydroorotate dehydrogenase

28
Q

what is the prodrug for 5 FU and what is the enzyme inhibited by this drug ?

A

capectabine
thymidylate synthase

29
Q

what are the after effects of giving azathioprine with another xanthine oxidase inhibitor ?

A

immunosuppression

30
Q

what enzyme is blocked by mycophenolate and ribavarin ?

A

inosine monophosphate dehydrogenase

31
Q

what enzyme is inhibited by cytosine arabinoside ?

A

DNA polymrase

32
Q

what turns UMP into dUMP ?

A

ribonucleotide reductase

33
Q

what diseases are treated hydroxyurea ?

A

polycythemia vera
essential thrombocytosis
sickle cell anemia

34
Q

what reaction does CPSII facilitate ?

A

glutamine to carbamoyl phosphate
CPSII stands for carbamoyl synthetase

35
Q

CPS1 vs CPS11 ?

A

cps1 is purely mitochondria ( hepatic )
cps2 is purely cytosolic

36
Q

in the pyrimidine synthesis process what process is inhibited by methotrexate and azathioprine ?

A

the conversion of PRPP to IMP

USMLE biochemistry (9 decks)

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